The formation of heterochromatin, which requires methylation of histone H3 at lysine 9 and the subsequent recruitment of chromodomain proteins such as heterochromatin protein HP1, serves as a model for the role of histone modifications and chromatin assembly in epigenetic control of the genome. Recent studies in Schizosaccharomyces pombe indicate that heterochromatin serves as a dynamic platform to recruit and spread a myriad of regulatory proteins across extended domains to control various chromosomal processes, including transcription, chromosome segregation and long-range chromatin interactions.
RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels. Here, we describe the purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission yeast. The RITS complex contains Ago1 (the fission yeast Argonaute homolog), Chp1 (a heterochromatin-associated chromodomain protein), and Tas3 (a novel protein). In addition, the complex contains small RNAs that require the Dicer ribonuclease for their production. These small RNAs are homologous to centromeric repeats and are required for the localization of RITS to heterochromatic domains. The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci.
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